Considerable work in this laboratory has focused on the role of enkephalin and dynorphin in seizure activity and related sequelae. Among other things, this work has implicated enkephalin as playing a major role in the elucidation of a phenomenon in rats known as "wet dog shakes" (WDS). This work has also implicated the dentate granule cells (DGCs) as being necessary for the elicitation of WDS at least with respect to induction by kainic acid or by stimulation of the perforant path (PP). The first objective of this project was to develop a method of electrical stimulation of the PP which would elicit WDS consistently and repeatedly in the absence of an overt seizure. Using this method, we have demonstrated that stimulation of the PP under conditions which elicit WDS produces a significant decrease in hippocampal levels of enkephalin and dynorphin. Levels of these substances are not altered by stimulus parameters insufficient to elicit WDS. Moreover, intraventricular injection of either an opioid mu receptor (beta- FNA) or delta receptor (ICIl74864) antagonist reduced the number of WDS elicited by PP stimulation. These data provide the first evidence that endogenous opioids are released by PP stimulation and lend further support to the notion that they play a role in regulation of hippocampal excitability. In addition, preliminary experiments suggest that dexamethazone increases the number of WDS following PP stimulation. Thus, a possible interaction between glucocorticoids and enkephalin is suggested and will be pursued. Other studies in progress concern (1) the relative contribution of the dorsal vs. ventral portions of the hippocampal formation in the phenomenon of WDS, and (2) whether or not there is a loss of recurrent inhibition on the DGCs before WDS can be elicited. Also, the effect of enkephalin on DGCs and basket cells will be examined in hippocampal slices and in hippocampal cells grown in culture in order to characterize the mechanism by which enkephalin affects these cells.